The US Food and Drug Administration granted acalabrutinib approval as the second Bruton tyrosine kinase (BTK) inhibitor to treat patients with chronic lymphocytic leukemia and small lymphocytic lymphoma as monotherapy or in combination with obinutuzumab. This approval was based on 2 phase 3 trials: ELEVATE-TN and ASCEND. There are several concerns with the design of these trials, including suboptimal treatment of patients in the control arm, expansion of the trial population, and lack of data regarding efficacy or tolerability compared with ibrutinib, a first-in-class drug. The Food and Drug Administration approval of acalabrutinib for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma represents concerning drug approval patterns in the United States and a weakness in evidence generation. 相似文献
Brain glioma is the most common malignant tumor of the central nervous system, and one of the leading causes of death in patients with intracranial tumors. The clinical outcome of glioma is usually poor due to abundant vascularity, fast growth and susceptibility of invasion to normal brain tissues. Our microarray study showed that lncRNA-LINC01116 was significantly upregulated in glioma tissues and played an important role in cell proliferation, cycle, migration, invasion and angiogenesis. In addition, vascular endothelial growth factor (VEGFA) may be the major target genes in the downstream of lncRNA-LINC01116. Dual luciferase assay showed that LINC01116 and VEGFA both contained a miR-31-5p binding site, and LINC01116 could regulate the expression of VEGFA through competitive absorption of miR-31-5p. RNA immunoprecipitation indicated that LINC01116 and VEGFA were present in the miR-31-5p-RISC complex, and biotinylated miR-31-5p pull-down assay suggested that there was a competitive relationship between LINC01116 and VEGFA to bind with miR-31-5p. Collectively, our study has identified a novel lncRNA-LINC01116 and clarified the role and mechanism of LINC01116 in the tumorigenesis of glioma. LINC01116 may prove to be a potential target for the clinical diagnosis and treatment of glioma. 相似文献
Background: Hyperthermia has proved successful in treating cutaneous human papillomavirus infectious diseases such as plantar wart and condyloma acuminata (CA). Moreover, this treatment provides improved therapeutic efficacy in these conditions as compared with conventional therapies.
Objectives: To investigate the global proteome changes in CA in response to hyperthermia and achieve a better understanding of the mechanisms of hyperthermia therapy against HPV-infectious diseases.
Methods: CA tissue was obtained from patients undergoing pathological examinations. Diagnosis was verified as based on results of both HE staining and HPV-DNA PCR assay. Hyperthermia was achieved with a 44?°C water bath. Differentially expressed proteins (DEPs) were identified by iTRAQ labeling, SCX chromatography and LC-MS/MS assay. Validation of proteomic results was performed using real-time qPCR and western blot, while bioinformatic analysis of DEPs was accomplished by R 3.4.1, STRING and Cytoscape softwares.
Results: In response to hyperthermia, a total of 102 DEPs were identified with 37 being upregulated and 65 downregulated. Among these DEPs, hyperthermia induced proteins involved with anti-viral processes such as OAS1, MX1, BANF1, CANX and AP1S1, whereas it inhibited proteins that participated in cellular metabolism, such as GALT, H6PD, EXOSC4 and EXOSC6; protein translation, such as RPS4Y1; as well as keratinocyte differentiation, such as KRT5, KRT27, KRT75, KRT76 and H2AFY2.
Conclusions: Hyperthermia inhibited enzymes and molecules responsible for metabolism modulation and keratinocyte differentiation in CA tissue, whereas it promoted factors involved in anti-viral responses. Such effects may, in part, contribute to the efficacy of local hyperthermia therapy against HPV infection. 相似文献
Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) have poor prognosis, and the efficacy of chemotherapy plus tyrosine kinase inhibitors (TKIs) followed by mismatched donor stem cell infusion (microtransplantation, MST) has not been determined. We retrospectively summarized 45 patients including 11 undergoing MST with TKIs, 17 receiving allogeneic transplant and 17 undergoing chemotherapy with TKIs. Improved 4-year overall survival rate was observed in the MST group (91%) compared with either transplant group (31%, P = .005) or chemotherapy group (36%, P = .013). The MST group also had higher 2-year and 4-year leukemia-free survival rates (91% and 72%, respectively) compared with either transplant group (33%, P = .005 and 33%, P = .021, respectively) or chemotherapy group (41%, P = .017 and 31%, P = .023, respectively). 2-year and 4-year cumulative incidences of hematologic relapse were lower in the MST group (9% and 28%, respectively) compared with those in the chemotherapy group (56%, P = .025 and 67%, P = .034, respectively). In patients undergoing MST, donor microchimerism was detected (1.07 × 10-5 to 6.6 × 10-4 copies from 9 to 1499 days) in 7 patients, and donor/patient-derived HLA*0201/2402+WT1+CD8+ T cells were found from 0.05% to 0.67% in 6 patients. MST may provide a favorable treatment for patients with Ph+ ALL. 相似文献
Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related death due to the failure of traditional therapies. In the present study, we attempted to construct a lncRNA-miRNA-mRNA network which may modulate PDAC cell proliferation and Gemcitabine-induced cell apoptosis starting from CDK14, a new member of the CDK family and an oncogene in many cancers. Based on TCGA data, a significant positive correlation was observed between lncRNA MSC-AS1 and CDK14. Moreover, MSC-AS1 expression was upregulated in PDAC tissues. Higher MSC-AS1 expression was correlated with poorer prognosis in patients with PDAC. MSC-AS1 knockdown in Panc-1 and BxPC-3 cells significantly inhibited the cell proliferation. Moreover, miR-29b-3p, which has been reported to act as a tumor suppressor, was predicted to bind to both MSC-AS1 and CDK14. Contrary to MSC-AS1, higher miR-29b-3p expression was correlated to better prognosis in patients with PDAC. In both PDAC cell lines, miR-29b-3p negatively regulated MSC-AS1 and CDK14. As confirmed using luciferase reporter gene and RIP assays, MSC-AS1 served as a ceRNA for miR-29b-3p to counteract miR-29b-mediated CDK14 repression. MSC-AS1 knockdown inhibited CDK14 protein levels and PDAC proliferation and enhanced gemcitabine-induced cell death and apoptosis while miR-29b-3p inhibition exerted an opposing effect; the effect of MSC-AS1 knockdown was partially attenuated by miR-29b-3p inhibition. Taken together, we demonstrated that MSC-AS1/miR-29b-3p axis modulates the cell proliferation and GEM-induced cell apoptosis in PDAC cell lines through CDK14. We provided a novel experimental basis for PDAC treatment from the perspective of lncRNA-miRNA-mRNA network. 相似文献